E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | pref |
E.1.2 | Classification code | 10058920 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to investigate the effects on RLS symptoms (based on IRLS) and sleep disturbance (based on MOS sleep scale) of pramipexole 0.125 mg/day to 0.75 mg/day per os for 12 weeks, compared to placebo, in the treatment of patients with idiopathic Restless Legs Syndrome (RLS). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to investigate the effects on clinical global impressions - global improvement (based on CGI-I responder rate), RLS (based on IRLS responder rate), other MOS dimensions (based on MOS sleep scale), daytime symptoms (based on items 4–6 of the RLS-6 scales), associated mood disturbance (based on item 10 of the IRLS scale), pain in limbs (based on a visual analogue scale), cognitive function (based on verbal fluency tests), quality of life in RLS (based on Johns Hopkins RLS-QoL questionnaire), patient global impression (based on PGI responder rate) and safety (based on AE profile) of pramipexole in comparison to placebo. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Written informed consent consistent with ICH-GCP and local IRB/IEC requirements obtained prior to any study procedures being performed and the ability and willingness to comply with study treatment regimen and to attend study assessments. 2.Male or female out-patients aged 18-80 years. 3.Diagnosis of idiopathic RLS according to the clinical RLS criteria of the IRLSSG. All four criteria must be present to fulfil the diagnosis of RLS: •An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. (Sometimes the urge to move is present without the uncomfortable sensations and sometimes the arms or other body parts are involved in addition to the legs) •The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting •The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues •The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night. (When symptoms are very severe, the worsening at night may not be noticeable but must have been previously present). 4.RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline (Visit 2). 5.IRLS total score >15 at baseline (Visit 2). |
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E.4 | Principal exclusion criteria |
1.Women of child-bearing potential (i.e. premenopausal women, or postmenopausal women less than 6 months after last menses) who do not use during the clinical trial an adequate method of contraception such as: double barrier protection (e.g. diaphragm or condom and spermicide), intrauterine device, hormonal therapy (oral, injectable, or subcutaneous), or partner’s surgical sterilization. 2.Any women of childbearing potential not having negative pregnancy test at screening. 3.Breastfeeding women. 4.Concomitant or previous pharmacologic therapy for RLS as follows: •Any intake of dopamine agonists within 14 days prior to baseline (Visit 2) •Any intake of levodopa within 14 days prior to baseline (Visit 2) •Any intake of levodopa prior to baseline visit, if augmentation in RLS symptoms was observed •Unsuccessful prior treatment with non-ergot dopamine agonists (e.g. pramipexole, ropinirole). 5.All treatment less than 14 days before baseline (Visit 2) or concomitant treatment with medication or dietary supplements which could significantly influence RLS symptoms, e.g. dopaminergic (other than levodopa and dopamine agonists) or antidopaminergic drugs, non-selective MAO inhibitors, sympathomimetics, neuroleptics, antidepressants, hypnotics, any benzodiazepines, antiepileptics, opioids, clonidine, ferrous salts, magnesium, folic acid, vitamin B12, antihistaminics, lithium, metoclopramide. 6.Withdrawal symptoms of any medication must not be present at baseline (Visit 2). 7.Previous pramipexole non-responders in other indications than RLS. 8.Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets. 9.Diagnosis of diabetes mellitus requiring insulin therapy. 10.Any of the following lab results at screening: •Patients with any clinically significant abnormalities in laboratory parameters at screening at the investigator’s discretion •Haemoglobin (Hb) below lower limit of normal (LLN). 11.Clinically significant renal disease or calculated creatinine clearance (CrCl) lower than 30 mL/minute at screening. 12.Clinically significant hepatic disease or GPT >2 times the upper limit of normal (ULN) at screening. 13.Serum ferritin <10 ng/mL at screening. 14.History of/or malignant melanoma. 15.History of/or clinically significant vision abnormalities. 16.History of/or any other sleep disorder (other than RLS-related), such as Rapid Eye Movement (REM) sleep disorder, narcolepsy or sleep apnoea syndrome. 17.History of/or major depressive disorder or any psychotic disorder, mental disorders or any present Axis I psychiatric disorder according to DSM IV requiring any medical therapy. 18.History of/or clinical signs of suicidal behaviour, suicide ideation or acute suicidal tendency according to the investigator’s opinion. 19.History of/or alcohol abuse or drug addiction within the last 2 years before screening. 20.Patients on a shift-work-schedule or who are otherwise unable to follow a regular sleep-wake cycle enabling use of study medication at times indicated. 21.Participation in an investigational drug study within one month prior to the start of this study. 22.Patients with any clinically significant conditions that in the opinion of the investigator would interfere with the evaluation of the results or constitute a health hazard for the patient according to SPC.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the change from baseline after 12 weeks of treatment in the total score of the International Restless Legs Syndrome Study Group Rating Scale (IRLS). Co-primary endpoint will be the change from baseline after 12 weeks of treatment in the MOS sleep disturbance score of the Medical Outcomes Study (MOS) sleep scale.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For the current protocol the “end of trial overall” is defined as the date of the last visit completed by the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |